The proposed research is aimed at (1) further definition of the molecular mechanisms of deoxy-Hb S polymerization and gelation, by mapping of intermolecular contact sites for each tetramer subunit, studies of the role of non S Hbs in polymerization, and the effect of Hb dissociation equilibria and hybrid formation in polymerization in red cells, and interactions of Hbs S and C; (2) further studies of functional properties of HbS-containing-red cells, (3) examination of the functional abnormalities (and their structural basis) of rbc membranes in SS, CC and other abnormal red cells. These studies are designed to further our knowledge of the mechanisms of sickling, to aid in the design and application of antisickling agents, to determine physiological conditions dangerous or favorable to persons with various sickling disorders, and to explore the pathophysiology of the red cell membranes with the overall aim of improving cell survival and function in these disorders.